Riccardo Marmo

Colorectal Cancer: CT Colonography and Colonoscopy for Detection—Systematic Review and Meta-Analysis

PURPOSE To perform a systematic review and meta-analysis of published studies assessing the sensitivity of both computed tomographic (CT) colonography and optical colonoscopy (OC) for colorectal cancer detection. MATERIALS AND METHODS Analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The primary data source was the results of a detailed PubMed search from 1994 to 2009. Diagnostic studies evaluating CT colonography detection of colorectal cancer were assessed by using predefined inclusion and exclusion criteria, in particular requiring both OC and histologic confirmation of disease. Studies that also included a mechanism to assess true-positive versus false-negative diagnoses at OC (eg, segmental unblinding) were used to calculate OC sensitivity. Assessment and data extraction were performed independently by two authors. Potential bias was ascertained by using Quality Assessment of Diagnostic Accuracy Studies guidelines. Specific CT colonography techniques were cataloged. Forest plots of per-patient sensitivity were produced on the basis of random-effect models. Potential bias across primary studies was assessed by using the I(2) statistic. Original study authors were contacted for data clarification when necessary. RESULTS Forty-nine studies provided data on 11,151 patients with a cumulative colorectal cancer prevalence of 3.6% (414 cancers). The sensitivity of CT colonography for colorectal cancer was 96.1% (398 of 414; 95% confidence interval [CI]: 93.8%, 97.7%). No heterogeneity (I(2) = 0%) was detected. No cancers were missed at CT colonography when both cathartic and tagging agents were combined in the bowel preparation. The sensitivity of OC for colorectal cancer, derived from a subset of 25 studies including 9223 patients, was 94.7% (178 of 188; 95% CI: 90.4%, 97.2%). A moderate degree of heterogeneity (I(2) = 50%) was present. CONCLUSION CT colonography is highly sensitive for colorectal cancer, especially when both cathartic and tagging agents are combined in the bowel preparation. Given the relatively low prevalence of colorectal cancer, primary CT colonography may be more suitable than OC for initial investigation of suspected colorectal cancer, assuming reasonable specificity. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101887/-/DC1.

Dual therapy versus monotherapy in the endoscopic treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials.

BACKGROUND:There is no definite recommendation on the use of dual endoscopic therapy in patients with severe peptic ulcer bleeding. A systematic review and meta-analysis were performed to determine whether the use of two endoscopic hemostatic procedures improved patient outcomes compared with monotherapy.METHODS:A search for randomized trials comparing dual therapy (i.e., epinephrine injection plus other injection or thermal or mechanical method) versus monotherapy (injection, thermal, or mechanical alone) was performed between 1990 and 2006. Heterogeneity between studies was tested with χ2 and explained by metaregression analysis.RESULTS:Twenty studies (2,472 patients) met inclusion criteria. Compared with controls, dual endoscopic therapy reduces the risk of recurrent bleeding (OR [odds ratio] 0.59 [0.44–0.80], P = 0.0001) and the risk of emergency surgery (OR 0.66 [0.49–0.89], P = 0.03) and showed a trend toward a reduction in the risk of death (OR 0.68 [0.46–1.02], P = 0.06). Subcategory analysis showed that dual therapy was significantly superior to injection therapy alone for all the outcomes considered, but failed to demonstrate that any combination of treatments is better than either mechanical therapy alone (OR 1.04 [0.45–2.45] for rebleeding, 0.49 [0.50–4.87] for surgery, and 1.28 [0.34–4.86] for death) or thermal therapy alone (OR 0.67 [0.40–1.20] for rebleeding, 0.89 [0.45–1.76] for surgery, and 0.51 [0.24–1.10] for death).CONCLUSIONS:Dual endoscopic therapy proved significantly superior to epinephrine injection alone, but had no advantage over thermal or mechanical monotherapy in improving the outcome of patients with high-risk peptic ulcer bleeding.

Mucosal Healing Predicts Late Outcomes After the First Course of Corticosteroids for Newly Diagnosed Ulcerative Colitis

BACKGROUND & AIMS It is uncertain whether mucosal healing after the first course of corticosteroids therapy predicts outcome in patients with ulcerative colitis (UC). We evaluated whether early clinical and endoscopic responses to this therapy are associated with late outcomes in UC. METHODS Patients with newly diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed up for 5 years. They were evaluated using clinical (Powel-Tuck [PT]) and endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at month 3 (early response) were used to identify patients with complete (group A: PT, 0-1; Baron, 0), partial (group B: PT, 0-1; Baron, 1-3), or no response (group C: persistence of clinical and endoscopic activity). The association between early and late outcomes was assessed. RESULTS After 5 years, there were significant differences between complete and partial responders in the rates of hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.21-6.72), immunosuppression therapy (5% in group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67-25.67), colectomy (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24-32.37), and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61; 95% CI, 1.12-6.11). After multivariate analysis, lack of mucosal healing was the only factor associated with negative outcomes at 5 years (immunosuppressors: hazard risk [HR], 10.581; 95% CI, 2.193-51.039; P = .0033; hospitalization: HR, 3.634; 95% CI, 1.556-8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278-55.186; P = .0268). CONCLUSIONS No mucosal healing after corticosteroid therapy is associated with a more aggressive disease course.

Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).

Effective bowel cleansing before colonoscopy: a randomized study of split-dosage versus non-split dosage regimens of high-volume versus low-volume polyethylene glycol solutions

BACKGROUND Adequate bowel cleansing is essential for a high-quality, effective, and safe colonoscopy. OBJECTIVES To evaluate the degree of colon cleansing comparing split-dosage versus non-split-dosage intake of two different polyethylene glycol (PEG) volumes (low-volume PEG + ascorbic acid vs standard-volume PEG-electrolyte solution) and to identify predictors of poor bowel cleansing. DESIGN Single-blind, active control, randomized study. SETTING Tertiary-care institutions in Italy. PATIENTS This study involved adult patients undergoing elective colonoscopy. INTERVENTION Colonoscopy with different bowel preparation methods. MAIN OUTCOME MEASUREMENTS Degree of bowel cleansing. RESULTS We randomized 895 patients, and 868 patients were finally included in intention-to-treat (ITT) analysis. Overall compliance was excellent (97%) for both preparation methods. No difference in tolerability was recorded. Palatability was superior with low volume compared with high volume (acceptable or good 58% vs 51%, respectively, P < .005), independently of intake schedule. PEG plus ascorbic acid produced the same degree of cleansing as standard-volume PEG-electrolyte solution (77% vs 73.4%, respectively, within the split-dosage group and 41.7% vs 44.3%, respectively, within the non-split-dosage group). Independently of PEG volumes, the split-dosage regimen produced markedly superior cleansing results over the same-day method (good/excellent 327/435, 75.2% vs 186/433, 43.0%, P = .00001). Maximum cleansing was observed in colonoscopies performed within 8 hours from the last fluid intake versus over 8 hours from the last fluid intake (P < .001). The degree of bowel cleansing affected both cecal intubation (failed intubation 11.7% with fair/poor preparation vs 1.2% with good/excellent preparation, P = .00001) and polyp detection rates (12.2% with fair/poor vs 24.6% with good/excellent preparation, P = .001). Aborted procedures were significantly more frequent in the non-split-dosage arm (21.2% vs 6.9%, odds ratio [OR] 3.60 [2.29-5.77], P < .0001). Independent predictors of poor bowel cleansing were male sex (OR 1.45 [1.08-1.96], P = .014) and a non-split-dosage bowel preparation schedule (OR 2.08 [1.89-2.37], P = .0001). CONCLUSION Low-volume PEG plus ascorbic acid is as effective as high-volume PEG-electrolyte solution but has superior palatability. A split-dosage schedule is the most effective bowel cleansing method. Colonoscopy should be performed within 8 hours of the last fluid intake.

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naïve to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

Predictive Factors of Mortality From Nonvariceal Upper Gastrointestinal Hemorrhage: A Multicenter Study

OBJECTIVES:From an Italian Registry of patients with upper gastrointestinal hemorrhage (UGIH), we assessed the clinical outcomes and explored the roles of clinical, endoscopic, and therapeutic factors on 30-day mortality in a real life setting.METHODS:Prospective analysis of consecutive patients endoscoped for UGIH at 23 community and tertiary care institutions from 2003 to 2004. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression analysis identified predictors of mortality.RESULTS:One thousand and twenty patients were included. A total of 46 patients died for an overall 4.5% mortality rate. In all, 85% of deaths were associated with one or more major comorbidity. Sixteen of 46 patients (35%) died within the first 24 h of the onset of bleeding. Of these, eight had been categorized as ASA class 1 or 2 and none of them was operated upon, despite a failure of endoscopic intention to treatment in four. Regression analysis showed advanced age, presence of severe comorbidity, low hemoglobin levels at presentation, and worsening health status as the only independent predictors of 30-day mortality (P < 0.001). The acute use of a PPI exerted a protective effect (OR 0.23, 95% CI 0.09–0.73). Recurrent bleeding was low (3.2%). Rebleeders accounted for only 11% of the total patients deceased (OR 3.27, 95% CI 1.5–11.2).CONCLUSIONS:These results indicate that 30-day mortality for nonvariceal bleeding is low. Deaths occurred predominantly in elderly patients with severe comorbidities or those with failure of endoscopic intention to treatment.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

Capsule Endoscopy Versus Enteroclysis in the Detection of Small-Bowel Involvement in Crohn’s Disease: A Prospective Trial

BACKGROUND & AIMS The aim of this study was to prospectively compare the diagnostic yield of wireless capsule endoscopy (WCE) and enteroclysis in evaluating the extent of small-bowel involvement in Crohns disease (CD). METHODS Thirty-one patients (20 men; mean age, 43 y) with endoscopically and histologically proven CD underwent enteroclysis as their initial examination, followed by WCE. The radiologist who performed the small-bowel enema was blinded to the results of standard index endoscopy, which included retrograde ileoscopy. Gastroenterologists were blinded to the results of enteroclysis at the time of interpretation of the WCE video. RESULTS Abnormal findings were documented in 8 of 31 patients by using enteroclysis and in 22 of 31 patients by using WCE (25.8% vs. 71%, P < .001). In 16 patients with known involvement of the terminal ileum, the diagnostic yield of WCE vs enteroclysis was significantly superior (89% vs 37%, P < .001). In 15 patients without lesions in the terminal ileum, abnormal findings in the proximal small bowel were detected in 7 (46%) patients by WCE and only in 2 (13%) patients by enteroclysis (P < .001). The capsule detected all but 2 lesions diagnosed by enteroclysis. WCE detected additional lesions that were not detected by enteroclysis in 45% of cases. CONCLUSIONS WCE is superior to enteroclysis in estimating the presence and extent of small-bowel CD. WCE may be a new gold standard for diagnosing ileal involvement in patients with CD without strictures and fistulae.

Predicting Mortality in Non-Variceal Upper Gastrointestinal Bleeders: Validation of the Italian PNED Score and Prospective Comparison With the Rockall Score

OBJECTIVES:We sought (i) to validate a new prediction rule of mortality (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to compare the accuracy of the Italian PNED score vs. the Rockall score in predicting the risk of death.METHODS:We conducted prospective validation of analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008. Outcome measure was 30-day mortality. All the variables used to calculate the Rockall score as well as those identified in the Italian predictive model were considered. Calibration of the model was tested using the χ2 goodness-of-fit and performance characteristics with receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of the two predictive models.RESULTS:Over a 16-month period, data on 1,360 patients were entered in a national database and analyzed. Peptic ulcer bleeding was recorded in 60.7% of cases. One or more comorbidities were present in 66% of patients. Endoscopic treatment was delivered in all high-risk patients followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six patients died (mortality 4.85%; 3.54–5.75). The PNED score showed a high discriminant capability and was significantly superior to the Rockall score in predicting the risk of death (AUC 0.81 (0.72–0.90) vs. 0.66 (0.60–0.72), P<0.000). Positive likelihood ratio for mortality in patients with a PNED risk score >8 was 16.05.CONCLUSIONS:The Italian 10-point score for the prediction of death was successfully validated in this independent population of patients with non-variceal gastrointestinal bleeding. The PNED score is accurate and superior to the Rockall score. Further external validation at the international level is needed.